2. RemeOs™ Screw is the first healthy
and absorbable metal implant in the
U.S market
2
Bioretec
RemeOs™ Screw LAG Solid
3. Definitions
• Biomaterial = A natural or synthetic material that is suitable for introduction into living tissue.
• Bioactivity = The ability of a material to interact with or effect any cell tissue in the human body. The ability of a
material to form a direct bond with the host biological tissue
• Biocompatibility = The ability of a material to perform with an appropriate host response in a specific situation.
The ability of a material to be in contact with a living system without producing an adverse effect.
• Osteointegration = The property of a material that allows the development of a direct, adherent and strong bond
with the surrounding bone tissue. The formation of a direct interface between an implant and bone, without
intervening soft tissue.
• Osteoconduction = The ability of a material to facilitate new bone formation by allowing bone cells to adhere,
proliferate, and form an extracellular matrix on its surface and pores. Primarily based on mechanical stimuli as well
as the chemical composition and geometry of the material.
• Osteopromotion = Describes a material that promotes the de novo formation of bone and needs an osseous
defect that provides nutrients (blood) to enhance bone growth. Effectively promotes new bone growth by
accelerating bone remodeling.
• Osteoinduction = The ability to induce new bone formation through molecular stimuli recruitment and
differentiation in a controlled phenotype or particular lineage promote cellular functions leading to new bone
formation
3
RemeOs™ material Science
4. Bone/Fracture healing
RemeOs™ material Science
• The central goal of any fracture treatment is to
restore bone continuity, thereby reinstating the
function of the affected extremity or body section
and alleviating pain1,2.
• A critical aspect in terms of orthopedic implants
is that they should not impede the natural
physiology of the bone healing process.
• Bone is a living tissue capable of self-repair
• Bone only forms when mechanical loading is
present and constantly adjusts itself in response to
physiological and mechanical changes(Wolff’s
law).3,4
• Bone is continuously being renewed; balance
between osteoblasts forming bone and osteoclasts
resorbing bone.5
• This process of constant bone resorption and bone
formation is called bone remodeling
• Osteoclasts break down and remove old and damaged
bone, whereas osteoblasts deposit new bone matrix that
subsequently becomes mineralized.
• Rebuilding bone following a fracture can be classified into
primary (direct) and secondary (indirect) healing.1
• Secondary (indirect) healing occurs in the vast majority of bone
injuries. It is typically characterized by distinct but overlapping stages:
a) hematoma formation and inflammation, b-c) repair, and d)
remodeling.
Following these initial phases, a
soft callus (fibrocartilaginous
callus) forms from the
granulation tissue
approximately 2–3 weeks after
fracture. When the fracture
ends are bridged by a soft
callus, Ca is deposited, leading
to the development of a hard
callus or woven bone. This hard
callus stage might persist for
about 12–16 weeks.
Damaged blood vessels
immediately lead to a
hematoma formation at
the fracture site, which is
gradually replaced during
the inflammatory phase
by fibrin rich granulation
tissue at 3–7 days post-
fracture. Osteoclasts start
to resorb the necrotic
bone at the fracture ends.
In the last step of fracture
repair, bone remodeling,
small bone fragments are
removed by osteoclasts,
while osteoblasts deposit
woven bone and then
convert it to lamellar bone.
Adapted from ref 2.
4
5. Magnesium in general
• Mg is well-suitable as a biodegradable implant material.
• It is an essential element for the human body and the fourth most
abundant cation (Mg2+) 6,7, with approximately 20–28 g in a healthy
adult human body8,9. About half of the total amount is stored within
the skeleton and positively influences bone strength10. Less than one
percent is found in the blood11. The remaining portion is bound in the
muscles and soft tissue. It plays a major role in membrane
stabilization, neuromuscular excitation, and central nervous system
functions12. It acts as a cofactor in almost all enzymatic systems,
stabilizes structures like DNA or RNA, and is involved in metabolic
pathways13.
• Excessive Mg ions are permissible as they can be transported via the
circulatory system and promptly excreted by way of urine and faces,
without causing any adverse effects.14
• Published studies suggest that the exposure of bone to a
degrading Mg implant exerts a positive impact on the biological
process of bone growth and regeneration. This is attributed to
locally high amounts of available Mg and stimulatory effects
such as osteoblastic differentiation, which in turn promotes
bone formation15-18. Mg ions integrate into the apatite crystal
lattice, enhancing cell adhesion and accelerating the growth of
bone tissue19-20.
5
RemeOs™ material Science
Daily dietary intake
360mg
Daily urinary output
100mg
Daily faecal output
260mg
INTESTINE
Absorption 120mg
Secretion 20mg
KIDNEY
Filtration 2400mg
Reabsorption 2300mg
BLOOD
COMPARTMENT
OTHER TISSUES
4900mg
MUSCLE
6600mg
Bone
12900mg
Adopted from ref 21.
6. RemeOs™ Magnesium alloy (Mg-Ca-Zn)
• Pure Mg is relatively weak and is almost exclusively used as an alloy for engineering and medical applications.22
• Material properties of Mg alloys can be adjusted by different alloying elements. With appropriate alloying elements,
the mechanical, physical, and electrochemical (degradation rate) properties can be improved and adapted, like
enhancing yield strength, ductility and controlling gas evolution.
• In terms of biomedical products, the choice of alloying elements is limited as the resulting by-products should exert
minimal effects on the body, must be non-toxic, and must be capable of either being absorbed by surrounding tissues
or dissolved and excreted naturally.23,24
• RemeOs™ alloying elements yielding together with Magnesium yield a HEALTHY implant :
• Calcium: Ca is a promising alloying element for absorbable Mg alloys due to its biocompatibility arising from its natural occurrence
within the human metabolism. It positively influences bone health and can help to accelerate growth and healing25,26. It has been
reported that Ca enhances both the mechanical properties and the corrosion resistance of Mg-based alloys27,28. The addition of Ca to
a Mg alloy results in grain refinement28,29, which is an effective method to enhance the strength by grain boundary hardening,
described by the Hall-Patch relationship30,31. Another notable advantage of Ca is its influence on elevated ductility26,32.
• Zinc: The yield strength of Mg alloys can be enhanced by adding Zn due to grain refinement33-35. One advantageous aspect of Zn as
an alloying element is its potential to decrease the amount of hydrogen gas evolution resulting from Mg corrosion24,36. Zn has been
observed to enhance osteoblastic cell proliferation and positively influence bone healing when used as an alloying element in Mg-
based biomaterials. Generally, Zn enhances the corrosion resistance of Mg alloys, but the effect varies based on the specific alloy
composition26.
6
RemeOs™ material Science
7. RemeOs™ bioactive and osteopromotive implants
are Mg alloy optimized to support bone healing
• RemeOs™ Magnesium – Calcium – Zinc
alloy has been designed to have a
controlled degradation rate through its
composition with controlled impurity
profile (Cu, Ni, Fe, Zr, and heavy metals) and
manufacturing process, yielding high
mechanical properties
• RemeOs™ alloy has a nominal content of
Ca 0.55 w-%, Zn 0.45 w-% with Mg
composing the rest
• Only with this proprietary composition, Ca is
able to form Mg2Ca intermetallic
precipitates, which act as a sacrificial anode,
protecting Mg-matrix from excess corrosion
• Biomechanical properties are closer to bone
(cortical) than traditional metals,
biopolymers, and composites
• Biomechanical properties have been
designed to retain strength over the bone
healing period without stress shielding and
which gradually diminishes through surface
degradation to allow bone to gain its
natural strength
7
RemeOs™ material Science
One drawback of classic non-
degradable metals (Ti, SS) is
their mismatch in mechanical
properties to bone. Bones need
mechanical stress produced by
everyday movements to become
ossified, retain their strength,
and regenerate (Wollf’s Law)3,4.
Metallic implants are notably
stiffer, with a Young’s modulus of
about 100–200 GPa as opposed
to 10–30 GPa for the human
bone37,38. This difference can
cause stress shielding, where the
stiffer implant mechanically
shields the bone tissue from
loading stresses. This effect can
cause bone atrophy and
osteolysis39-41, resulting in altered
bone morphology42 and a
general delay in the healing
process39.
8. Degradation of Magnesium alloy
• The mechanism of the degradation (absorption) of magnesium and its alloys is a complex multifactorial phenomenon
depending on various parameters like geometry, mechanical and chemical composition (nature and ratio of alloying
elements), and interactions with the physiological environment
• Pure Mg is one of the most electronegative engineering materials, possessing a low standard potential of -2.37 V 43,44.
Therefore, it is highly susceptible to degradation in various environments, including the physiological conditions within the
body 45,46. The degradation process of Mg is an electrochemical process in the aqueous environment
• The degradation (absorption) proceeds electrochemically as follows: The anodically initiated Mg dissolution occurs according to Equation
(1). This counterbalances the cathodic reaction, wherein the hydrogen gas develops (Equation (2)). The product formation of Mg(OH)2
proceeds electrochemically according to Equation (3).47
Mg → Mg+ 2e− (1)
2H2O + 2e − → H2 + 2OH− (2)
Mg2+ + 2OH− → Mg(OH)2 (3)
• The total degradation (absorption) reaction of Mg in aqueous environments can be given, in which Mg(OH)2 forms a protective layer
around the implant while hydrogen gas (H2) is produced (4).47
Mg(s) + 2H2O(aq) → Mg(OH)2(s) + H2(g) (4)
• To meet the requirement of a medical implant, degradation (absorption) resistance must be enhanced by adding alloying
elements to slow down the degradation rate and increase implant stability.
8
RemeOs™ material Science
9. Degradation of Magnesium alloy
• The presence of inorganic salts in the physiological solutions
of the human body increases the complexity of the
degradation of Magnesium alloys.
• The degradation of magnesium alloys forms a degradation
zone on top of the magnesium alloy implant in accordance
with the following chemical reactions.47
Mg(s) + 2H2O(aq) → Mg(OH)2(s) + H2(g)
OH- + HCO3
- → CO3
2- + H2O
Mg2+ + CO3
2- → MgCO3 (s)
H2PO4
- / HPO4
2- + OH- → PO4
3- + H20
3Mg2+ + 2PO4
3- → Mg3 (PO4)2 (s)
Ca2+ + CO3
2- → CaCO3 (s)
3Ca2+ + 2PO4
3- → Ca3(PO4)2 (s)
• The main intermediate product deposits on the degradation
zone are Mg(OH)2, MgCO3, Mg3(PO4)2, CaCO3, and
Ca3(PO4)2.48,49
9
RemeOs™ material Science
The degradation zone at a pH value of approximately 7.4
(in vivo conditions) is neither stable nor complete and
will continuously be dissolved50 but forms a bioactive
hydroxy apatite (HA) layer for cells to attach.
Mg2+
H2
Mg(OH)2
H2O
HCO3-
CO3
2-
Ca2+ PO4
3-
Hydroxy apatite
layer HA
Ca3(PO4)2
Mg3(PO4)2 CaCO3
Physiological conditions
Biomineralization
MgCO3
Mg alloy implant
10. Verification of degradation zone in Mg-Ca-Zn
• The Mg-doped Calcium and Phosphorous rich
hydroxyapatite layer HA (degradation zone) is formed due
to the degrading implant and has been examined using
SEM-EDX (rat, 24 weeks) in a sample cross-section.
• The SEM image shows the morphology of the bone-implant
interface, and the black rectangle outlines the interfacial region
of investigation for EDX.
• The elemental profile was measured from top to bottom along
the dashed line (top, left panel), indicating the presence of the
degradation zone as Mg/O-rich.
• It shows a gradual increase in Ca and P levels toward the bone.
I. denotes the implant region,
II. corresponds to the initial degradation layer,
III. designates the second layer in the degradation zone
referred to as the direct bone-implant interface, and
IV. represents the bone tissue.
10
RemeOs™ material Science
Mg is represented in yellow, O in purple, Ca in pink, and P in green.
Adopted from ref 51.
11. Biological interface
• Mg alloys have been defined as a type of biomaterial that
have osteopromotive52 effects due to their degradation
products.
• Studies have shown that Mg degradation products can
enhance osteogenesis, inhibit catabolic activity and osteoclast
differentiation, and promote osteoblast adhesion and motility
to facilitate bone recovery
• Mg2+ stimulates the osteogenic differentiation of stem cells with
selective activation of the MAPK/ERK pathway53. The MAPK/ERK
pathway is one of the signaling pathways governing the
osteogenic differentiation of stem cells.
• Mg2+ enhances the mineralization of the extracellular matrix (ECM)
by increasing the production of collagen-X and vascular
endothelial growth factor (VEGF).54
• The high concentration of Mg2+ and high pH, reduces the fusion of
pre-osteoclast cells and the activity of osteoclasts, thereby
inhibiting osteoclastogenesis.55
• Vessel development is vital for bone formation, and Mg2+ can
promote angiogenesis by stimulating VEGF, angiogenin and other
crucial chemoattractants.56
• Mg plays a multifunctional role in bone growth and
regeneration. It exerts both direct and indirect effects
between connecting bone, vessels, nerves, and immune
systems, creating potential for functional bone regeneration.51
RemeOs™ material Science
Degradation
zone / Mg-
Doped HA
layer
Mg
alloy
implant
Periosteum
Cortical Bone
Trabecular Bone
Medullary Cavity
Periosteal stem cells (PSCs)
Bone marrow stem cells (BMSCs)
Differentiation
Differentiation
Osteoblast-like cells
Osteoblast-like cells
Osteoclast
Pre-osteoclast
Monocytes of vascular/
bone marrow origin
Migration along bone surface
Migration along
trabeculae
High Mg2+
reduces cell
fusion
High pH
reduces
resorption
Mg2+ concentration
The effects of Mg in the biological interface have been comprehensively investigated using both in vitro and in
vivo models 57-60
12. Osteopromotion of RemeOs Mg alloy In Vivo
Enhanced bone growth verified in
large animal studies
• Strong new bone growth (callus
formation) was observed as early as 6
weeks, and in 12 weeks, the RemeOs™
screw was overgrown with new bone
(green circle)
• No biological activity within the Titanium
control group at the 6 weeks or 12 weeks
timepoint (orange circle)
• The corrosion behavior of low-alloyed
Mg-Ca-Zn is characterized by a slow and
controlled homogenous degradation.
Furthermore, implants showed excellent
biocompatibility, new bone formation,
and established a robust implant-bone
interface.61
12
RemeOs™ material Science
6
weeks
12
weeks
RemeOs™ Titanium
13. Long term large animal study in large animal shows
osteointegration and homogeneous resorption
13
RemeOs™ material Science
Long-term 2 years large animal
study in sheep of Mg-Ca-Zn 3.5
mm screw shows surface
resorption and new bone
formation. 62
Total degradation time depends
on the screw size (surface
degradation), complete
resorption is around 2-3 years.
(A-C) Histologic evaluation of the 24-mm ZX00 screw after the
25-month period in sheep tibiae with (D) respective micro-CT. 62
(A) New bone formation, “bony bridges,” within the medullary
cavity is marked with a black arrow, and reactive woven
bone formation on the periosteum adjacent to the screw
head is marked with a white asterisk.
(B) Osteocytes and osteoblasts are marked with black and
white arrowheads, respectively.
(C) The fat necrosis area is shown with white arrows, and gas
pockets are marked with black asterisks (Laczko-Levai
stain; original magnification, x10).
14. The Role of degradation product H2
• Degradation within the aqueous environment of the body is highly complex.
Controlling the degradation rate is challenging and plays a fundamental role in bone
formation. The actual corrosion rate in the body varies depending on several factors,
like the pH of body fluids, the concentration and types of ions present, the presence
of proteins, temperature, impurities in the metal, alloying elements, and the
surrounding tissue.
• The process of Mg degradation is always accompanied by hydrogen gas evolution,
and the rate of gas formation directly depends on the degradation rate of the alloy.
• The role of degradation products H2 in the biological interface is not completely
clear. Thus, H2 plays a significant role in the regulation of the local microenvironment
and the biology of resident cells and may inhibit osteoclast formation.63
• It has been postulated that a slow hydrogen evolution rate of 0.01 ml/cm2/day could
be tolerated by the body painlessly without causing severe harm if the gas can be
transported away from the site of its generation.22
• If the local hydrogen saturation of blood and tissue is reached, diffusion and
solubility of hydrogen in surrounding tissues become hindered. Then hydrogen gas
can accumulate and create gas voids in the tissue around the implantation site.
• Therefore, adjusting the degradation rate, and consequently the rate of gas
accumulation, through appropriate alloying elements is essential.
14
RemeOs™ material Science
Schematic description of the degradation
process and H2 avolution under in vitro
conditions. a) electrochemical reactions, b)
absorption-desorption process, c) mass transfer
processes, d) precipitation reactions, e)
complexation reactions, f) acid-base reactions
15. Degradation zone and H2 gas evolution
28/11/23
15
RemeOs™ material Science
OP 2 weeks 6 weeks 12 weeks 24 weeks
Degradation zone and H2 gas evolution
The preclinical and clinical studies have shown that the degradation zone build-up and gas evolution start immediately after
the implantation and are most prominent during first few weeks and start to slow down after 6 weeks, and start to decrease
at 12 weeks, with the fracture healed after 6 weeks (no visible fracture line in 12- & 24-weeks time points)62,64,65
Fracture healing
16. In vivo strength retention over healing period
16
RemeOs™ material Science
12weeks
6 weeks
0 weeks
• Strength retention over 12 weeks in vivo has
been demonstrated in a large animal model
with no statistical difference between
implantation and 12 weeks pullout force (p =
0.08, ⍶ = 0.05)
• No effect of degradation products (including
H2) on the strength retention
• According to the in vitro – in vivo (IVIVC)
correlation, 12 weeks in large animals
corresponds to min 30 weeks in human
high resolution micro-computed tomography
In Vivo Pull-out testing in large animal model
Data on File
17. RemeOs™ screw Surgical technique & MRI
compatibility
• Surgical technique similar to conventional metal implants
• Self-tapping and easy insertion
• Compression performance and fixation strength comparable to conventional metal implants
• X-rays, CT or MRI can be used to evaluate the healing of the tissue.
• The implants are MR Conditional. Imaging may demonstrate implant-associated radiolucent areas related to device absorption
(hydrogen gas formation). Based on the MGAS Clinical Study, these abnormalities typically begin to decrease) at around 12 weeks and are
not clinically significant. (FDA Instructions for use: BIORETEC RemeOs™ Screw LAG Solid IFU Rev. 1.0 2023-05-05)
• Malleolar Fracture Fixation (typically 2 screws)
17
RemeOs™ material Science
Drill the K-wire into the bone to keep the fracture
in position and to mark the prescribed path for
the cannulated screw.
Countersink (optional). Use the countersink to
make space for the screw head and to avoid soft
tissue irritation from the protruding screw head.
Drill a screw channel through the fracture plane
using the appropriate drill bit. Irrigate prior to
screw insertion to flush out bone debris.
Hold the screwdriver and the screw parallel to
the long axis of the drill hole and insert the screw
fully into the drill hole.
18. Safety and Efficacy of absorbable metal
verified in clinical trial
18
RemeOs™ material Science
◼ Indication: Medial malleolar fracture fixation
◼ Patient enrollment: 20 patients through 12 weeks follow-
up, 18 patients up to 130 weeks follow-up
All primary end points achieved 62,64,65
◼ In 6 weeks, 90% of the fractures were healed
◼ After 12 weeks complete consolidation in all patients
◼ No adverse events or intraoperative complications
◼ All patients regained mobility in the ankle joint
◼ No pain in any of the patients after 6 weeks
◼ Normal levels of Mg and Ca in blood
◼ Normal wound healing; no swelling, erythema, oedema
nor infections
◼ No loosening of the implant nor clinical implications
due to the H2 gas evolution
OUTCOME: Fractures stabilized and healed in all patients
Patients with medial malleolar fractures: pre-operative to after surgery
Of the patients who also received Titanium implants, 71% of the Titanium hardware
had to be removed
Female,
47y
Male,
30y
Female,
64y
19. Degradation zone in patient radiographs
RemeOs™ material Science
PRE-OP WEEK 2 WEEK 6 WEEK 12 WEEK 24 WEEK 52 WEEK 130
Female,
47y
RemeOsTM screw visible (blue arrow)
Degradation zone including gas
evolution (white arrow)
The syndesmosis
screw was removed
at week 6, and its
hole (orange arrow)
is visible in the
cortex after week
130
Full absorption
of the screw at
week 130.
20. Hole from Titanium syndesmosis screw
Removal (removed at 6 week timepoint)
Although radiographs revealed a homogeneous bone texture, CT slices revealed gaps at the Mg-Zn-Ca screw site in the
trabecular bone, which may be because of recent resorption that has not been remodeled yet and may only be
resolved with a longer bone remodeling period62. Bone only forms where it is needed when mechanical loading is
present (Wolff’s law).3,4
Male,
30
years
old,
130
weeks
Full degradation within 130 weeks and
ongoing bone remodeling
RemeOs™ material Science
20
CT slice video
21. FDA confirmed benefits of RemeOs™ trauma
screw and material*
21
RemeOs™ material Science
Excellent biocompatibility
= Safe
Bioactive, osteopromotive properties
= Enhanced bone growth
Fixation strength comparable with conventional metal implants
= No screw loosening due to gas evolution
The RemeOsTM bioresorbable
metal is composed of natural
elements found in the human
body Magnesium (Mg), Calcium
(Ca) and Zinc (Zn) Easy insertion and use, comparable to conventional metal implants
= Common surgical techniques
Rapid bone ingrowth, regeneration, and replacement
= Makes removal operations redundant
Strength retention tailored to match the bone healing
= Carries the load over the healing period
In this release the term (bio)resorbable is interchangeable with
(bio)absorbable and (bio)degradable
* RemeOs™ Risk analysis in FDA granted De Novo request
22. FDA De Novo decision – The First RemeOs™
indication is for the Ankle and Foot area
22
RemeOs™ material Science
DEVICE DESCRIPTION*: The implants are constructed of an absorbable magnesium-based alloy
containing magnesium, zinc and calcium. The material is composed of natural elements found
in the human body (Mg alloy with a nominal content of Ca 0.55 w-% and Zn 0.45 w-%). The
material corrodes under physiological conditions into magnesium, calcium and zinc oxides and
hydroxides, which are naturally occurring elements and compounds in the human body and are
known to promote new bone growth. Hydrogen gas, which is a byproduct of the corrosion
process, may contribute to transient bone lucency that is radiographically observable. The
material has high initial mechanical strength and stiffness. Implants made from this material have
similar biomechanical characteristics (E modulus, tensile strength) to those of natural
(cortical) bone. When properly used, in the presence of adequate immobilization, the implants
maintain accurate alignment of medial malleolus fractures, and osteotomies, after surgical
procedure.
INTENDED USE: RemeOs™ Screw LAG Solid is intended for the use in traumatic and orthopedic surgery for the
fixation of bone fractures (osteosynthesis) and for the fixation after osteotomies, e.g., for the correction of deformities
or malalignments. The absorbable implants serve as temporary fixation and stabilization by osteosynthesis of bone
fractures and osteotomies until bony fusion has occurred. The RemeOs™ Screw LAG Solid is intended to be used for
skeletally mature adults.
INDICATED USE: The RemeOs™ Screw LAG Solid is indicated for the fixation of the medial malleolus. *
*FDA approved instructions for use (IFU)
In this release the term (bio)resorbable is interchangeable with (bio)absorbable and (bio)degradable
23. Clinical application of Mg based absorbable
metal for fracture fixation in the adult
skeleton
Patients with a full set of X-rays (pre-op, 2, 6, 12, 24, 52, 130 weeks follow-up)
Data on File (Clinical Trial)
24. 24
OP 6w
2W 24w
12w 52w 130w
Female, 47 years old
Male, 30 years old
OP 6w
2W 24w
12w 52w 130w
Female, 64 years old
OP 6w
2W 24w
12w 52w 130w
25. 25
Male, 43 years old
OP 6w
2W 24w
12w 52w 130w
OP 6w
2W 24w
12w 52w 130w
Male, 46 years old
Male, 29 years old
OP 6w
2W 24w
12w 52w 130w
26. 26
OP 6w
2W 24w
12w 52w 130w
Male, 56 years old
Male, 35 years old
OP 6w
2W 24w
12w 52w 130w
Female, 45 years old
OP 6w
2W 24w
12w 52w 130w
35. 35
CT scan Video
Removal hole of Titanium
syndesmosis screw
(removed at 6 week)
Although radiographs revealed a homogeneous bone texture, CT
slices revealed gaps at the implant site in the trabecular bone,
which may be because of recent resorption that has not been
remodeled yet and may only be resolved with a longer bone
remodeling period. 62
130 weeks, CT scan
Male, 30 years old
93. Reference List
1. B. Gueorguiev-Rüegg and M. Stoddart. Biology and biomechanics in bone healing. In R. E. Buckley, C. G. Moran, and T. Apivatthakakul, editors, AO principles of fracture management, volume 1, chapter 1.2, pages
9–26. Thieme, Stuttgart, DE, 3rd edition, 2018.
2. F. U. Niethard, J. Pfeil, and P. Biberthaler. Grundlagen der Unfallchirurgie. In Duale Reihe Orthop.die und Unfallchirurgie, chapter 10, pages 292–356. Thieme, Stuttgart, DE, 8th edition, 2017.
3. J. Wolff. Das Gesetz der Transformation der Knochen. Hirschwald, Berlin, DE, 1892.
4. N. Little, B. Rogers, and M. Flannery. Bone formation, remodelling and healing.Surgery, 29(4):141–145, 2011.
5. X. Feng and J. M. McDonald. Disorders of bone remodeling. Annu. Rev. Pathol.,6:121–145, 2011.
6. U. Gr.ber, J. Schmidt, and K. Kisters. Magnesium in prevention and therapy. Nutrients, 7(9):8199–8226, 2015.
7. A. M. Al Alawi, S. W. Majoni, and H. Falhammar. Magnesium and human health: Perspectives and research directions. Int. J. Endocrinol., 2018:1–17, 2018.
8. A. C. Ross, B. Caballero, R. J. Cousins, et al. Modern nutrition in health and disease. Wolters Kluwer Health/Lippincott Williams and Wilkins, Philadelphia, PA, 11th edition, 2014.
9. S. Schaal, K. Kunsch, and S. Kunsch. Der Mensch in Zahlen: Eine Datensammlung in Tabellen mit über 20000 Einzelwerten. Springer, Heidelberg, DE, 4th edition, 2016.
10. E. Ko., M. B. Kannan, M. .nal, and E. Candan. Influence of zinc on the microstructure, mechanical properties and in vitro corrosion behavior of magnesium–zinc binary alloys. J. Alloys Compd., 648:291–296, 2015.
11. P. M.hnle and A. E. Goetz. Physiologische Effekte, Pharmakologie und Indikationen zur Gabe von Magnesium. Anaesthesist, 50:377–391, 2001.
12. J. M. Seitz, R. Eifler, F. W. Bach, and H. J. Maier. Magnesium degradation products: Effects on tissue and human metabolism. J. Biomed. Mater. Res. A, 102(10):3744–3753, 2014.
13. A. Hartwig. Role of magnesium in genomic stability. Mutat. Res., 475(1-2):113–121, 2001.
14. A. Yamamoto, S. Hiromoto, Mater. Sci. Eng., C 2009, 29, 1559.
15. T. A. Grünewald, H. Rennhofer, B. Hesse, et al. Magnesium from bioresorbable implants: Distribution and impact on the nano- and mineral structure of bone. Biomaterials, 76:250–260, 2016.
16. J. Zhang, C. Xu, Y. Jing, et al. New horizon for high performance Mg-based biomaterial with uniform degradation behavior: Formation of stacking faults. Sci. Rep., 5(1):1–16, 2015.
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